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Ligand‐independent activation of vascular endothelial growth factor receptor 1 by low‐density lipoprotein
Author(s) -
Usui Ryosuke,
Shibuya Masabumi,
Ishibashi Shun,
Maru Yoshiro
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7401103
Subject(s) - ldl receptor , endocytosis , receptor , low density lipoprotein , chemistry , lipoprotein , endocrinology , medicine , microbiology and biotechnology , biology , cancer research , cholesterol , biochemistry
Elevated serum low‐density lipoprotein (LDL) is a risk factor for atherosclerotic disorders. However, prominent atherosclerosis, which has been observed in LDL receptor (LDLR)‐knockout mice, has diminished the significance of LDLR as a cause of atherosclerosis, while elaborate studies have focused on the receptors for denatured LDL. Here we report that native LDL (nLDL) activates vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) but not VEGFR2 through LDLR and is as potent as VEGF in macrophage migration. Binding and co‐endocytosis of VEGFR1 and LDLR were enhanced by nLDL, which is concomitant with ubiquitination‐mediated degradation of VEGFR1. We propose that LDLR‐mediated use of VEGFR1 by nLDL could be a potential therapeutic target in atherosclerotic disorders.